tbuckley/cabot-search huggingface dataset:
Abstract ED2-3: Hormonal exposure and risk in BRCA1/2 carriers
Authors: Joanne Kotsopoulos
Journal: Cancer Research (2023)

Abstract Women who inherit a pathogenic variant (mutation hereafter) in the BRCA1 or BRCA2 geneface extremely high lifetime risks of developing breast and ovarian (or fallopian tube) cancer. More than two decades since the discovery of these genes, and primary prevention with bilateral mastectomy and salpingo-oophorectomy remain the most effective options to manage cancer risk in this population. Understanding the impact of exogenous hormone use is important for both the clinical management of high-risk women and for furthering our knowledge of the pathogenesis of BRCA-associated disease. In this session, I will review the current epidemiologic data surrounding the role of exogenous (anti)hormone use on BRCA-cancer risk. Specifically, I will discuss the role of tamoxifen in preventing BRCA-associated breast cancer and I will describe whether use of oral contraceptives or hormone replacement therapy (HRT) increase the risk of breast cancer. Where possible, I will present data by gene mutation. Potential associations with the risk of ovarian cancer will also be referred to, given that managing BRCA-cancer risks is a balancing act. Finally, I will review how the epidemiologic information has contributed to the discovery of novel targets for the non-surgical prevention of BRCA1-associated breast cancer and gaps in the literature to be addressed in future research. Citation Format: Joanne Kotsopoulos. Hormonal exposure and risk in BRCA1/2 carriers [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED2-3.
Abstract ED9-3: Effects of age on the tumor microenvironment
Authors: Sandra McAllister
Journal: Cancer Research (2023)

Abstract Dr. McAllister’s translational research group studies breast cancer as a systemic disease with an emphasis on the role of immune fitness in disease control and response to therapy. In this education session, Dr. McAllister will introduce the concept of “immunological age”. She will discuss her team’s ongoing efforts to understand how age sets the stage for triple-negative breast cancer (TNBC) progression and response to immune checkpoint blockade therapy. Her team was the first to report that bone marrow derived immune cells from 8–10-week-old young mice promote more aggressive TNBC growth when transferred to 12–15-month-old aged mice (Marsh, et al., Cancer Research, 2016). They subsequently identified cellular and molecular mechanisms that promote aggressive disease, as typically observed in younger individuals. Likewise, her group was the first to report that immune checkpoint blockade therapy is less effective in older mice with TNBC and discovered a treatment strategy that improved outcomes in pre-clinical TNBC models (Sceneay, et al., Cancer Discovery, 2019). The same tumor cellular and molecular pathways that stratified by age in their pre-clinical models also defined age-stratified differences between younger (under 40) and older (over 65) TNBC patients in the METABRIC dataset. She will present her team’s new work on functional aspects of immunological age in TNBC and the ongoing efforts of the Older Women with Breast Cancer Research and Treatment Team at the Dana-Farber/Brigham Cancer Center. Ultimately, she and her team wish to eliminate age- and race-based disparities in breast cancer outcomes. Citation Format: Sandra McAllister. Effects of age on the tumor microenvironment [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED9-3.
Abstract OT1-14-01: Efficiency and safety of palbociclib in patients with locally advanced or metastatic breast cancer: a muti-center real world study
Authors: Yongmei Yin, Xiang huang, Wei Li, Xinyu Wu, Yijia Hua, Chunxiao Sun
Journal: Cancer Research (2023)

Abstract Endocrine therapy is the main treatment for premenopausal women with HR+/HER2- breast cancer. Palbociclib is an oral CDK4/6 inhibitor which preclinical evidence that ER+ and HER2-amplified breast cancer cell lines are most sensitive to CDK4/6 inhibition of proliferation and is used in vitro in combination with endocrine therapy showed better tumor suppressive effect. To evaluate the efficacy and safety of palbociclib in patients with locally advanced or metastatic breast cancer, we enrolled females with hormone receptor-positive breast cancer who treat with Palbociclib from July 2018 to March 2022. The study has so far included 267 patients in 4 centers. 32.83% patients were treated in first-line, 31.32% and 38.85% patients in second and third lines. 30.34% patients had hepatic metastasis. 35.47% patients were sensitive to previous endocrine therapy; 18.23% patients had primary resistance to endocrine therapy, while 46.31% patients had secondary resistance to endocrine therapy. The median PFS was 12.67 months (95% CI 11.51-13.92), and Median overall survival (OS) was not reached. Among all patients, the overall response rate (ORR) was 25.84%, and the disease control rate (DCR) was 78.62%. The main adverse events related to treatment were neutropenia (91.38%), white blood cell decreased (90.09%), anemia (43.78%), and thrombocytopenia (37.93%). The most common grade 3/4 adverse event was neutropenia (55.61%). 11.99% of patients had dose reductions. More patients still needed for further analyze. Citation Format: Yongmei Yin, Xiang huang, Wei Li, Xinyu Wu, Yijia Hua, Chunxiao Sun. Efficiency and safety of palbociclib in patients with locally advanced or metastatic breast cancer: a muti-center real world study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-14-01.
Abstract P1-07-08: Prediction of breast cancer late recurrence according to Clinical Treatment Score post-five years (CTS5) and progesterone receptor in a wider patient population
Authors: Giselle S. Carvalho, GUSTAVO O. BRETAS, Daniel Musse, Victor Gondim, José Bines
Journal: Cancer Research (2023)

Abstract Background The duration of adjuvant endocrine therapy remains a continuous challenge in hormone-receptor positive (HR+) early breast cancer. The Clinical Treatment Score post-five years (CTS5) is an online model used to predict late distant metastasis for women with HR+ breast cancer who are recurrence-free 5 years after endocrine therapy (ET). It incorporates patients age, tumor size, grade, and number of positive lymph nodes, and is an important tool to help in this treatment decision. There is a paucity of data in premenopausal women and whether other variables could add additional information. Methods A single-center retrospective analysis of patients that have received adjuvant ET for 5 years, between January 2007 and December 2008 at the Instituto Nacional de Cancer (INCA), Brazil. Disease-Free Survival (DFS) was compared between the low, intermediate, and high-risk subgroups. Data analysis was descriptive and exploratory. Kaplan-Meier estimates and Cox regression models were used. Results A total of 183 patients were enrolled, 26.5% being premenopausal. Median age at diagnosis was 66 years. Tumor stage: I (44%) and II (56%). ET consisted of tamoxifen (88%), anastrozol (6%), and a switch (6%). There were 39.5%, 39.5% and 21% of patients in the low, intermediate, and high-risk (L/I/H) subgroups, respectively. Progesterone-receptor was ≥ 20% in 71% of tumors and in 55%, 49% and 34% in the L/I/H subgroups, respectively. Median follow up was 88.9 months. After 5 years, the median DFS was 100%, 96.3% and 68.2% in L/I/H subgroups (p &amp;lt; 0,001). Progesterone-receptor was also an independent prognostic factor for late recurrence (p &amp;lt; 0,05). Conclusion CTS5 performed well in a wider patient population including premenopausal women. Progesterone-receptor was an independent prognostic factor for DFS and should be further considered into the model. Citation Format: Giselle S. Carvalho, GUSTAVO O. BRETAS, Daniel Musse, Victor Gondim, José Bines. Prediction of breast cancer late recurrence according to Clinical Treatment Score post-five years (CTS5) and progesterone receptor in a wider patient population [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-07-08.
Abstract ED3-1: Updates in the pathology of PABC
Authors: Kalliopi Siziopikou
Journal: Cancer Research (2023)

Abstract Updates in the Pathology of Pregnancy Associated Breast Cancer (PABC) Pregnancy associated breast cancer is defined as a breast cancer diagnosed during gestation, lactation and within 1 to 5 years postpartum. While the development of malignancy during pregnancy is rare, the incidence is increasing; breast cancer is one of the most common cancers diagnosed during pregnancy and the postpartum period occurring in up to 1 in 3000 deliveries. Of interest, breast cancer is the leading cause of cancer death in US women age 15-29. Pregnancy has a dual effect on breast cancer development: on one hand cancer protective and on the other cancer promoting. While a number of hypotheses have been proposed over the years to explain these effects, the most likely hypothesis for the development of PABC is the involution hypothesis. This hypothesis proposes that the involution pathways activated during pregnancy and the immediate postpartum period are remodeling programs similar to wound healing and inflammation that may be associated with tumor development and progression. Although PABCs can be any subtype of breast carcinomas, they are usually invasive ductal carcinomas of high tumor grade and large tumor size with higher stage at presentation and higher rates of lymph node involvement. Most PABCs are hormone receptor negative tumors with high Ki-67 proliferation rates; most frequently, they are either triple negative or HER2-positive carcinomas. A number of studies have shown that PABCs have different genomic signatures than the non-PABC tumors with PABCs having an increased expression of immune response mediators. Better understanding of the molecular pathways of tumor initiation and progression and prompt diagnosis and state-of-art treatment protocols in PABC is expected to lead to better outcomes for these young breast cancer patients. Citation Format: Kalliopi Siziopikou. Updates in the pathology of PABC [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED3-1.
Abstract MS2-3: Implications for clinical care
Authors: Alexandra Thomas
Journal: Cancer Research (2023)

Abstract Late recurrence, commonly considered to be distant recurrence five or more years after initial diagnosis remains a formidable challenge in breast oncology. Current management focuses on slowing the growth of macroscopic recurrent disease which is generally considered incurable. Emerging tools to identify minimal residual disease or tumor dormancy hold great promise to transform the treatment landscape in this space. This mini-symposium discussion will review the scope of the clinical challenge, highlighting the numbers at risk and the timeframe for recurrence risk. Current and emerging tools to assess the risk in individual patients beyond 5 years from diagnosis will be discussed. Evidence and guidelines on the use of clinically available anatomic-based and genomic assay-based late risk assessment tools including Clinical Treatment Score post-5 years (CTS5) and the Breast Cancer Index (BCI) will be highlighted. Current data on the role of circulating biomarkers including ctDNA, to identify at risk patients will be discussed as will open questions on how this might impact treatment approach. Finally, possible therapeutic approaches following the identification minimal residual or dormant disease will be reviewed, as will trial design options in this rapidly evolving space in breast oncology. Citation Format: Alexandra Thomas. Implications for clinical care [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr MS2-3.
Abstract P1-10-15: Concious sparing of contralateral thyroid lobe in Ca Breast patients receiving post mastectomy radiotherapy by IMRT technique – A single institution dosimetric study
Authors: Manish Chomal, Minaal Iyer, Ananth Kalimurthy, Joshua Sahay, Sushanta Banik
Journal: Cancer Research (2023)

Abstract Purpose/Objective(s): The purpose of this paper is to report the dosimetric effects of conscious sparing of contralateral lobe of thyroid gland in carcinoma breast patient receiving locoregional radiation by tangential beam Intensity Modulated radiotherapy technique. Materials/Methods: Treatment plans of 20 Ca Breast patients, who received post mastectomy adjuvant locoregional radiotherapy, were evaluated. Since October 2021 we adopted a department protocol of conscious sparing of contralateral thyroid in breast radiotherapy. 10 of these had conscious sparing of contralateral thyroid (group A) whereas 10 of old plans were evaluated when C/L thyroid were not given constraints &amp; are being passively spared due to location on contralateral/non treatment side of neck (group B). Treatment planning was done using tangential beam (6 MV) IMRT in Eclipse 13.7 TPS in all of these patients. All of these patients received treatment to chest wall &amp; SCF. RTOG contouring guidelines were followed in all the patients. Prescription Dose was 40Gy in 15# for both groups. The best treatment plans were selected ensuring 95% PTV dose coverage and acceptable dose to OARs. Uniform contouring, plan optimization &amp; evaluation protocols were followed for all of these patients. Results: The mean thyroid volume in group A is 4.30cc &amp; in group B is 3.99cc which is not statistically different (P value -0.639) The mean dose of thyroid in group A is 7.98Gy whereas in group B it is 17.00Gy which is spastically significant (P value – 0.000003). Comparison of mean dose to contralateral lobe (in Gy) between the two groups Groups No. Mean ± SD ‘t’ value P value Thyroid dose with constraint 10 7.98±1.46 -6.702, df=18 0.000003* Thyroid dose without constraint 10 17.00±3.99 Unpaired ‘t’ test applied. P value = 0.000003, Significant Conclusion: OARs present on contralateral side are passively spared due to the location. This often results in a tendency of not actively prescribing constraints to these. This study emphasizes that conscious sparing of contralateral Thyroid lobe can further reduce the dose to significant levels. This reduction can preserve thyroid function further. Further clinical trials are required to corroborate this dosimetric gain with clinical thyroid function preservation. Citation Format: Manish Chomal, Minaal Iyer, Ananth Kalimurthy, Joshua Sahay, Sushanta Banik. Concious sparing of contralateral thyroid lobe in Ca Breast patients receiving post mastectomy radiotherapy by IMRT technique – A single institution dosimetric study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-15.
Abstract ED9-2: The contribution of the tumor microenvironment to cancer dormancy
Authors: Jose Javier Bravo-Cordero
Journal: Cancer Research (2023)

Abstract In this seminar I will discuss how breast cancer DTCs modify the metastatic microenvironment to favor seeding and dormancy. In order to extravasate efficiently and form metastasis, cancer cells have to become migratory and coordinate both invasive and proliferative programs at distant organs. High-resolution lattice light-sheet with adaptive optics imaging in living cells revealed that DTCs extravasate from the blood vessels by forming actin-rich invadopodium protrusions. We have identified a population of breast cancer DTCs with pro-invasive and pro-dormancy capacities. These cells downregulate srGAP1, a GTPase regulator, favoring dissemination and dormancy at metastatic organs. Our findings describe a novel mechanism mediating the shift from a proliferative to an invasive/dormant phenotype in breast cancer cells in vivo. srGAP1 is a new regulator of dormancy that regulates the formation of dormancy-permissive microenvironments through increased secretion of TGFb2 and SMAD2 activation. Citation Format: Jose Javier Bravo-Cordero. The contribution of the tumor microenvironment to cancer dormancy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED9-2.
Abstract P1-11-06: Multi-omics profiling of HER2-low breast cancer reveals clinically relevant subgroups and therapeutic pathways
Authors: Lie Chen, Cui-Cui Liu, Jing-Yu Ge, Zhi-Ming Shao, Ke-da Yu
Journal: Cancer Research (2023)

Abstract The current HER2 testing algorithm can distinguish tumors that are completely negative for HER2 (IHC 0, HER2-zero) from HER2-low tumors [low (IHC 1+) or moderate expression (IHC 2+, ISH-)]. Because HER2-zero cases have often been combined with HER2-low cases, the clinical and biological understanding of HER2-low tumors is limited. To provide complementary information and shed light on the molecular characteristics and therapeutic insights of HER2-low breast cancer, we performed this multi-omics study of hormone receptor (HR)-negative and HER2-low breast cancer, also known as HER2-low triple-negative breast cancer (TNBC), and identified three subgroups: basal-like (BSL), receptor tyrosine kinase relevant (TKR), and mesenchymal stem-like (MSL). These three subgroups had distinct features and potential therapeutic targets and were validated in external datasets. Interestingly, the TKR subgroup (which exists in both HR-positive and HR-negative breast cancer) had activated HER2 and downstream MAPK signaling. In vitro and in vivo patient-derived xenograft experiments revealed that pretreatment with tyrosine kinase inhibitor (Lapatinib or Tucatinib) could inhibit HER2-signaling and induce accumulated expression of nonfunctional HER2 via a feedback loop, resulting in increased sensitivity to sequential HER2-targeting antibody-drug conjugate DS-8201. Our findings identify clinically relevant subgroups and provide potential therapeutic strategies for the previously targetless HER2-low TNBC subtype. GRAPH ABSTRACT Highlights of characteristics of HR-negative and HER2-low breast cancer subgroups Table S1. Highlights of characteristics of HR-negative and HER2-low breast cancer subgroups. Citation Format: Lie Chen, Cui-Cui Liu, Jing-Yu Ge, Zhi-Ming Shao, Ke-da Yu. Multi-omics profiling of HER2-low breast cancer reveals clinically relevant subgroups and therapeutic pathways [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-11-06.
Abstract OT2-18-03: Neoadjuvant anlotinib plus nab-paclitaxel based chemotherapy in patients with HER2-negative breast cancer: A prospective, single-arm, single-center, phase II clinical study
Authors: Jing Fan, Ting Wang, Huimin Meng, Songpeng Li, Jing Kong, Yidi Wang
Journal: Cancer Research (2023)

Abstract BACKGROUND: Antiangiogenic agent plus neoadjuvant chemotherapy confers an improvement in pathological complete response (pCR) rate among patients with HER2-negative breast cancer. Anlotinib is a novel multi-target tyrosine kinase inhibitor that effectively inhibit VEGFR, FGFR, c-KIT, c-MET, and RET. This phase II study aims to evaluate the efficacy and safety of anlotinib combined with chemotherapy as neoadjuvant treatment in HER2-negative breast cancer. PATIENTS AND METHODS: Eligible patients (pts) were women, aged 18-70 years, ECOG status 0-2, previously untreated HER2-negative breast cancer. The HER2-negative, defined as immunohistochemistry of 0, 1+, and 2+/ISH-. Pts were required to have a palpable primary tumor at least 200mm in diameter in the breast, as assessed by physical examination, and to be classified as having tumor stage T1c to T3, nodal stage N0 to N2a, and metastasis stage M0. Thirty pts will be enrolled and received 5 cycles of anlotinib (12 mg qd, d1-14; 21 days per cycle) plus 6 cycles of nab-paclitaxel (200 mg/m2, once every 3 weeks), anthracycline (pirarubicin 50 mg/m2) and cyclophosphamide at 500 mg/m2, followed by surgery. The primary endpoint is pCR rate (ypT0/Tis ypN0) and the secondary endpoints include disease-free survival (DFS), overall survival (OS), and safety. The study was initiated in August 2021.This study is currently open and 10 patients had been enrolled. The estimated primary completion date is October 1, 2023. Results: The trail is in progress. Conclusion: The trail is in progress. Citation Format: Jing Fan, Ting Wang, Huimin Meng, Songpeng Li, Jing Kong, Yidi Wang. Neoadjuvant anlotinib plus nab-paclitaxel based chemotherapy in patients with HER2-negative breast cancer: A prospective, single-arm, single-center, phase II clinical study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-18-03.
Abstract P1-06-07: Interrogating the Molecular Profile of Breast Cancer Tumors in Hispanics Living in Puerto Rico (PRH)
Authors: Norianne Martinez-Viota, Xavier Bittman-Soto, Ingrid M. Montes-Rodriguez, Kelvin Carrasquillo, Hilmaris Centeno-Girona, Marcia Cruz-Correa
Journal: Cancer Research (2023)

Abstract Breast cancer (BC) has the highest incidence and mortality rates among Puerto Rican women. However, the representation of Hispanics living in Puerto Rico (PRH) in breast cancer clinical trials may be limited due to the lack of a defined genetic profile from BC tumors in Puerto Rican patients. Mutations in genes associated with tumor suppressors, tumor progression, and genome stability are shared among all BCs. Nonetheless, differences in the frequency of these mutations have been observed among racial/ethnic groups. This study aims to characterize the genomic landscape of BC tumors in PRH and identify the most common genetic mutations. We conducted secondary data analysis to evaluate the mutational profile of 189 BC tumors from PRH who underwent NGS testing from 2015 to 2020 and compared the prevalence of breast tumor somatic mutations and gene amplifications with profiles reported for other races/ethnicities available through The Cancer Genome Atlas (TCGA) and the AACR Genomics Evidence Neoplasia Information Exchange (GENIE). The most mutated genes among PRH breast tumors were TP53, PIK3CA, ARID1A, NF1, and RB1, while the most frequent gene amplifications were FGF19, H3F3B, ZN703, MCL1, and ADGRA2. H1047R and E545K were the most frequent specific mutations in PRH for PIK3CA; R248Q and R273C for TP53 and Q1212*, S634* and Q557fs for ARID1A. Statistically significant differences were found between populations. This study reports a unique mutational profile of BC tumors in PRH and makes comparisons with non-Hispanic and USH populations, providing novel knowledge to increase Hispanic representation in future BC studies and treatments. Citation Format: Norianne Martinez-Viota, Xavier Bittman-Soto, Ingrid M. Montes-Rodriguez, Kelvin Carrasquillo, Hilmaris Centeno-Girona, Marcia Cruz-Correa. Interrogating the Molecular Profile of Breast Cancer Tumors in Hispanics Living in Puerto Rico (PRH) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-06-07.